title: Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic model.
abstract: The aim of this work was to analyze the atazanavir-bilirubin relationship, using a new mathematical approach to pharmacokinetic-pharmacodynamic models, for competitive drug interactions based on Michaelis-Menten equations.
  
  
  
  Because atazanavir induces an increase of plasma bilirubin levels, in a concentration-dependent manner, we developed a mathematical model, based on increments of atazanavir and bilirubin concentrations at steady state, in HIV infected (HIV(+)) patients, and plotted the corresponding nomogram for detecting suboptimal atazanavir exposure.
  
  
  
  By applying the obtained model, the results indicate that an absolute value or an increment of bilirubin at steady state below 3.8 μmol/L, are predictive of suboptimal atazanavir exposure and therapeutic failure.
  
  
  
  We have successfully implemented a new mathematical approach to pharmacokinetic-pharmacodynamic model for atazanavir-bilirubin interaction. As a result, we found that bilirubin plasma levels constitute a good marker of exposure to atazanavir and of viral suppression.
authors.affiliation: Pharmacy Department, Hospital Real Nuestra, Señora de Gracia.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lozano
authors.forename: Nieves
authors.initials: N
authors.lastname: Domeque
authors.forename: Alberto-Fermin
authors.initials: AF
authors.lastname: Apesteguia
keywords: HIV/AIDS; atazanavir; bilirubin; pharmacodynamics; pharmacokinetics